Trial News: Ketamine Drug Shows Great Promise in Treating Depression
Some people with depression do not respond enough, or at all, to standard anti-depression drugs. For these people the recent development of treatments based on the drug ketamine have shown great promise. After a series of clinical trials, the pharmaceutical giant Johnson & Johnson is seeking government approval (in the U.S. and European Union) for its version of ketamine – esketamine (Ketanest). The trials show that the drug is effective for treating people with severe depression (including suicidal tendencies).
These results, though not especially surprising, are somewhat controversial. Part of the controversy stems from the history of ketamine. The drug is a synthetic, first developed in 1965 as a derivative of phencyclidine (PCP), which is well known as a powerful psychotropic. Like PCP, ketamine is a “dissociative” anesthetic, meaning that it’s most prominent effect is reducing awareness through hallucination. While its main medical usage is as an anesthetic, it didn’t take long for it to become an alternative to the exceedingly dangerous use of PCP. It’s called “Special K” in the underground drug market and is relatively common in the drug-oriented party scene.
Despite the ‘recreational’ associations and sometimes unsavory history of ketamine use, the World Health Organization places ketamine on the list of “essential drugs” that all medically mature countries should have readily available. It is still frequently used as the anesthetic of choice in emergency situations because it suppresses breathing much less than many other anesthetics and slightly raises blood pressure and heart rate. It is, for example, often used in combat and natural disaster conditions.
Ketamine and the many derivatives have found an extremely wide variety of uses. With anesthesia as the basic application, it’s also used for treatment of asthmatics, pediatric anesthesia, topical anesthetic (such as lidocaine for dental work), veterinary anesthesia, and in low dosage for a painkiller (analgesic).
The Johnson & Johnson variant is also low dose. Administered through a nasal spray, esketamine does not have the anesthetic or hallucigenic properties of the original ketamine. Instead, esketamine affects the neural pathways in the brain. Researchers at Yale University described the effect as “rejuvenating the connections between brain cells (at the synapses) that have been damaged by stress and depression.”
Technically, the main difference between ketamine and esketamine is the way its molecules are organized. Although by chemical formula the two drugs are the same, they have a different molecular orientation. In chemistry and physics, this orientation is known as ‘handedness’ (left or right hand for the direction of molecular spin) or ‘chirality.’ Esketamine is an S-enantiomer, chemical jargon for a mirror image of the ketamine molecule but with a right-handed orientation. While this difference may seem slight, in practice it can mean subtle but important differences in effect. While ketamine in most normal doses is a true anesthetic, esketamine in similar doses is, at most, analgesic (painkilling) and psychogenic.
One of the main benefits of esketamine (and other ketamine-based drugs) for depression is their quick action. Typically, anti-depressives take days if not several weeks to produce noticeable effects. Esketamine can take effect within hours.
Johnson & Johnson and other manufacturers of similar ketamine-based products for psychological treatment expect that it will require several more years before these drugs are approved for commercial application. Their potency and potential for both short term and long term side effects make them tricky to formulate for targeted psychological uses. Esketamine will be a controlled-substance drug, available only by prescription and in limited amounts. (It already has an illegal drug market application.) It will probably remain an ‘alternative drug,’ used only when standard anti-depressants have little or no effect.
Still, the optimism level for esketamine and other ketamine-based drugs is high. There is a considerable amount of research headed in the direction of further, more targeted, derivatives that remove some of the more virulent side effects but retain specific psychological effectiveness.